Most cells exist in tissues in contact or even surrounded by an extracellular matrix composed of collagens, glycoproteins, and proteoglycans. The interactions of the cells with the tissue specific extracellular matrix components are important in the regulation of cell behavior. Our understanding of how the cells adhere to, grow on, migrate to, and differentiate on the extracellular matrix has been enhanced by the ability to purify the components and to test their biological effects both in vivo and in vitro. Specific molecules have been found which mediate the cellular responses both in matrix and on the cell surface. For example, laminin promotes the adhesion and growth of various epithelial cells while it appears to have a negative action of these activities for fibroblastic cells. We are currently investigating the biological activity of certain domains of the laminin molecule using synthetic peptides and domain and chain- specific antibodies. Specific adhesion and neurite promoting peptides have been identified which also disrupt endothelial cell differentiation. Our studies indicate that laminin has separate active sites for cell attachment and for neurite outgrowth. We are also determining the laminin receptors and tumor cell surfaces using molecular biological and biochemical approaches.